A rat model developed in our laboratory in which dehydroepiandrosterone (DHA) administration causes a premature ovulation followed by ovulatory failure and polycystic ovaries will be studied in detail. Attempts will be made to determine whether DHA or a particular conversion product of DHA is responsible for the ovulatory failure by studying the circulating blood steroids and correlation with gonadotropin during ovulatory failure induced by DHA administration and the reversal of such failure on androgen withdrawal. If the conversion of DHA to estradiol is solely responsible for the ovulatory failure, then low dose estrogen administration should suppress ovulation and this will be tried. Morphometric studies will be done with hypothalamic and pituitary tissues to study the effect of DHA and its conversion products on the synthetic apparatus, packaging and energy sources within the cell and the size and number of secretory granules in the gonadotropes. The sensitivity changes of the pituitary to synthetic LHRF will be studied after DHA treatment. The effect of DHA and its conversion products will be studied on the number of high-affinity binding sites for estradiol in the hypothalamus and pituitary as well as possible interference with estrogen binding. The direct effect of DHA and its conversion products on the process of ovulation will be studied and likewise their effect on ovarian steroidogenesis. Correlation between circulating steroids and gonadotropins will be attempted in the human in hyperandrogenic states before and after adrenal suppression, before, during and after removal of the virilizing tumor or wedge-resection of the polycystic ovary. BIBLIOGRAPHIC REFERENCES: Dehydroepiandrosterone-induced Polycystic Ovaries and Acyclicity in the Rat. James F. Knudsen, A. Costoff and V.B. Mahesh. Fertility & Sterility 26: 807-817, 1975. Initiation of Precocious Sexual Maturation in the Immature Rat Treated With Dehydroepiandrosterone. James F. Knudsen and V.B. Mahesh. Endocrinology 97:458-468, 1975.